1. Field
The present invention relates to a sustained-release preparation comprising a bioactive substance having an acidic group and a biodegradable polymer having an optionally protected basic group.
2. Description of the Related Art
To develop an excellent sustained-release preparation comprising a bioactive substance, various attempts have been made in the field of the manufacturing pharmacy, in consideration of the physical properties of the substance. A currently available method of preparing a sustained-release preparation of a bioactive substance having an acidic group is described in Japanese Patent Unexamined Publication No. 124814/1990, in which an acidic water-soluble drug is encapsuled in a microcapsule having a polymer as the wall material and incorporating a basic substance as a drug-retaining agent.
The Journal of the Korean Chemical Society, Vol. 34, No. 2, pp. 203-210 (1990) describes as a synthesis intermediate a compound wherein 3-amino-1-propanol is bound to the terminal carboxyl group of poly(1-lactide) via ester linkage.
The Journal of Macromol Chem., 196, 3891-3903(1995) discloses a poly(L-lactic acid)--OCH.sub.2 CH.sub.2 CH.sub.2 --NH.sub.2 and synthesis thereof as a initiator for the polymerization of N-carboxyanhydrides in the synthesis of poly(L-lactide)-block-poly(.alpha.-amino acid)s.
J. POLYM. SCI. PART A: POLYM. CHEM., 31, 275-278(1993) discloses .omega.-amino poly(.epsilon.-caprolactone) as a synthesis intermediate.
WO 94/21229 describes an aerosol composition containing a dispersion aid comprising a polymer having an amino acid bound to at least one terminal.
Although serving well as bases for sustained-release preparations of basic drugs, biodegradable polymers such as lactic acid-glycolic acid copolymer are unsatisfactory in terms of bioactivity retention, incorporation rate, suppression of drug leakage early after administration, constant sustained release for an extended period of time, and others, as bases for sustained-release preparations of bioactive substances having an acidic group.